INSULIN
Overview 
 Four major organs 
play a dominant role 
in fuel metabolism. 
 Integration of energy 
metabolism is controlled 
primarily by the actions 
of 
insulin and glucagon.
 Polypeptide hormone 
produce by the beta 
cells of the islet of 
Langerhans of the 
pancreas. 
 Most important 
hormone coordinating 
the use of fuels by 
tissues. 
 Metabolic effects-anabolic 
Favoring the synthesis 
of 
glycogen, 
triacylglycerols
 51 amino acids. 
 Polypeptide A and B, 
linked together by 
disulfide bonds. 
 Intramolecular 
disulfide bridge 
between amino acid 
residues of the A 
chain.
Synthesis of insulin 
 2 inactive precursors cleave to form active 
hormone and C – peptide. C – peptide is 
essential for proper insulin folding.
Stimulation of insulin secretion 
 Insulin and glucagon 
secretion is closely 
coordinated at the 
islet of Langerhans. 
 Secretion is regulated 
so that the rate of 
hepatic glucose 
production is kept 
equal to the use of 
glucose by peripheral 
tissues.
Stimulation of Insulin secretion is increased 
by Glucose. 
 ß cells contain Glut-2 
transporters and have 
glucokinase activity and 
thus can phosphorylate 
glucose in amounts 
proportional to itsactual 
concentration in blood. 
 Ingestion of CHO rich 
meal leads to a rise in 
blood glucose, which is 
a signal for insulin 
secretion and decrease 
glucagon synthesis and 
release.
Stimulation of Insulin secretion is stimulated 
by Amino Acid 
 Ingestion of protein 
causes a transient rise 
in plasma amino acids 
level, which in turn 
induces the secretion of 
insulin. 
 Elevated plasma 
arginine stimulates 
insulin secretion.
Stimulation of Insulin secretion increased by 
Gastro- Intestinal hormones. 
 Cholecytoskinin and 
gastric-inhibitory 
peptide increased 
insulin secretion. 
 Released from SI in 
response to oral 
glucose and cause 
anticipatory rise in 
insulin levels. 
 This may account for 
the fact that the same 
amount of glucose 
given orally induces a 
much greater secretion
Inhibition of insulin secretion: Epinephrine. 
 Scarcity of dietary fuels 
and during the period of 
stress, 
 Direct effect on energy 
metabolism 
 causing glycogenolysis 
and 
 Gluconeogenesis, 
 Can override the normal 
glucose- 
 stimulated release of 
insulin, 
 In emergency situation, 
the sympathetic nervous 
system largely replaces 
the plasma glucose 
concentration as the 
controlling influence over 
ß cells Secretion.
Metabolic effects of insulin : Carbohydrate 
metabolism. 
 Promotes storage in 3 
tissues-- 
 In liver & muscle, 
increase glycogen 
synthesis. 
 In muscle and 
adipose,increase 
glucose uptake by more 
GLUT-4. 
 Insulin decreased the 
production of glucose 
by inhibiting 
glycogenolysis and 
gluconeogenesis.
GLUT – 4 Transport protein
Metabolic effects of insulin- lipid 
metabolism 
 Decrease TAG 
degradation. 
Insulin inhibits hormone 
sensitive lipase , 
 Increaes TAG 
synthesis. 
Insulin increases 
transport and 
metabolism of glucose 
into adipocytes 
providing substrate for 
glycerol -3- phosphate 
for TAG synthesis. 
Also increases the 
lipoprotein lipase,thus
Metabolic effects of insulin : Protein 
synthesis. 
 Insulin stimulates the entry of amino acids into 
cells, and protein synthesis through activation of 
factors required for translation.
Membrane effects of Insulin.
Receptor regulation 
 Binding of insulin is 
followed by 
internalization of the 
hormone-receptor 
complex. 
 Once inside the cell, the 
insulin is degraded in 
the lysosomes. 
 The receptors may be 
degraded but most are 
recycled to the cell 
surface,
Characteristics of glucose transport in 
various tissues,
Diabetes Mellitus 
 Type I 
 Insulin dependent 
 Juvenile onset 
 Causes-- 
-Increased blood glucose (300-1,200 
mg/100ml) 
-Increased blood fatty acids and 
cholesterol 
-Protein depletion 
 Treated with insulin injections 
 Increases risk of heart disease and stroke 
 Can cause acidosis and coma
 Type II 
 Non-insulin dependent. 
Results from insulin insensitivity. 
 Elevated insulin levels. 
 Associated with obesity. 
Can lead to insulin dependent form. 
 Treated with weight loss, diet restriction, exercise 
and drugs.
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Insulin

  • 1.
  • 2.
    Overview  Fourmajor organs play a dominant role in fuel metabolism.  Integration of energy metabolism is controlled primarily by the actions of insulin and glucagon.
  • 3.
     Polypeptide hormone produce by the beta cells of the islet of Langerhans of the pancreas.  Most important hormone coordinating the use of fuels by tissues.  Metabolic effects-anabolic Favoring the synthesis of glycogen, triacylglycerols
  • 4.
     51 aminoacids.  Polypeptide A and B, linked together by disulfide bonds.  Intramolecular disulfide bridge between amino acid residues of the A chain.
  • 5.
    Synthesis of insulin  2 inactive precursors cleave to form active hormone and C – peptide. C – peptide is essential for proper insulin folding.
  • 7.
    Stimulation of insulinsecretion  Insulin and glucagon secretion is closely coordinated at the islet of Langerhans.  Secretion is regulated so that the rate of hepatic glucose production is kept equal to the use of glucose by peripheral tissues.
  • 8.
    Stimulation of Insulinsecretion is increased by Glucose.  ß cells contain Glut-2 transporters and have glucokinase activity and thus can phosphorylate glucose in amounts proportional to itsactual concentration in blood.  Ingestion of CHO rich meal leads to a rise in blood glucose, which is a signal for insulin secretion and decrease glucagon synthesis and release.
  • 9.
    Stimulation of Insulinsecretion is stimulated by Amino Acid  Ingestion of protein causes a transient rise in plasma amino acids level, which in turn induces the secretion of insulin.  Elevated plasma arginine stimulates insulin secretion.
  • 10.
    Stimulation of Insulinsecretion increased by Gastro- Intestinal hormones.  Cholecytoskinin and gastric-inhibitory peptide increased insulin secretion.  Released from SI in response to oral glucose and cause anticipatory rise in insulin levels.  This may account for the fact that the same amount of glucose given orally induces a much greater secretion
  • 11.
    Inhibition of insulinsecretion: Epinephrine.  Scarcity of dietary fuels and during the period of stress,  Direct effect on energy metabolism  causing glycogenolysis and  Gluconeogenesis,  Can override the normal glucose-  stimulated release of insulin,  In emergency situation, the sympathetic nervous system largely replaces the plasma glucose concentration as the controlling influence over ß cells Secretion.
  • 12.
    Metabolic effects ofinsulin : Carbohydrate metabolism.  Promotes storage in 3 tissues--  In liver & muscle, increase glycogen synthesis.  In muscle and adipose,increase glucose uptake by more GLUT-4.  Insulin decreased the production of glucose by inhibiting glycogenolysis and gluconeogenesis.
  • 13.
    GLUT – 4Transport protein
  • 14.
    Metabolic effects ofinsulin- lipid metabolism  Decrease TAG degradation. Insulin inhibits hormone sensitive lipase ,  Increaes TAG synthesis. Insulin increases transport and metabolism of glucose into adipocytes providing substrate for glycerol -3- phosphate for TAG synthesis. Also increases the lipoprotein lipase,thus
  • 15.
    Metabolic effects ofinsulin : Protein synthesis.  Insulin stimulates the entry of amino acids into cells, and protein synthesis through activation of factors required for translation.
  • 16.
  • 17.
    Receptor regulation Binding of insulin is followed by internalization of the hormone-receptor complex.  Once inside the cell, the insulin is degraded in the lysosomes.  The receptors may be degraded but most are recycled to the cell surface,
  • 18.
    Characteristics of glucosetransport in various tissues,
  • 21.
    Diabetes Mellitus Type I  Insulin dependent  Juvenile onset  Causes-- -Increased blood glucose (300-1,200 mg/100ml) -Increased blood fatty acids and cholesterol -Protein depletion  Treated with insulin injections  Increases risk of heart disease and stroke  Can cause acidosis and coma
  • 23.
     Type II  Non-insulin dependent. Results from insulin insensitivity.  Elevated insulin levels.  Associated with obesity. Can lead to insulin dependent form.  Treated with weight loss, diet restriction, exercise and drugs.
  • 29.